IR@PKUHSC  > 北京大学第二临床医学院
学科主题临床医学
A Genome-Wide Association Study Identifies GRK5 and RASGRP1 as Type 2 Diabetes Loci in Chinese Hans
Li, Huaixing1,2; Gan, Wei1,2; Lu, Ling1,2; Dong, Xiao2,3; Han, Xueyao4; Hu, Cheng5; Yang, Zhen6; Sun, Liang7,8; Bao, Wei9,10; Li, Pengtao11; He, Meian10,12; Sun, Liangdan13,14,15; Wang, Yiqin1,2; Zhu, Jingwen1,2; Ning, Qianqian2,3; Tang, Yong4; Zhang, Rong5; Wen, Jie6; Wang, Di9,10; Zhu, Xilin11; Guo, Kunquan10,12; Zuo, Xianbo13,14,15; Guo, Xiaohui18; Yang, Handong16,17; Zhou, Xianghai4; Zhang, Xuejun13,14,15; Qi, Lu19; Loos, Ruth J. F.20,21; Hu, Frank B.19; Wu, Tangchun10,12; Liu, Ying11; Liu, Liegang9,10; Yang, Ze7,8; Hu, Renming6; Jia, Weiping5; Ji, Linong4; Li, Yixue2,3,22,23; Lin, Xu1,2; DIAGRAM Consortium1; AGEN-T2D Consortium1
刊名DIABETES
2013
DOI10.2337/db12-0454
62期:1页:291-298
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]PANCREATIC BETA-CELL ; SUSCEPTIBILITY LOCI ; RECEPTOR ; POPULATION ; PHOSPHORYLATION ; INFLAMMATION ; VARIANTS ; GLUCOSE ; DIFFERENTIATION ; INTERNALIZATION
英文摘要

Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 x 10(-9)) and RASGRP1 (rs7403531: P = 3.9 x 10-9), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c), and lower homeostasis model assessment of beta-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility. Diabetes 62:291-298, 2013

语种英语
WOS记录号WOS:000312824700038
项目编号2009AA022704 ; 2011CB504002 ; 81021002 ; 81170734 ; 81170735 ; KSCX2-EW-R-10
资助机构National High Technology Research and Development Program of China (863 Program) ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; Chinese Academy of Sciences
引用统计
被引频次:81[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53234
专题北京大学第二临床医学院
作者单位1.Peking Univ, Hosp 1, Beijing 100871, Peoples R China
2.Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA
3.Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China
4.Minist Hlth, Beijing Inst Geriatr, Beijing, Peoples R China
5.Beijing Hosp, Key Lab Geriatr, Beijing, Peoples R China
6.Hubei Univ Med, Shiyan, Hubei, Peoples R China
7.Dongfeng Motor Corp, Dongfeng Cent Hosp, Shiyan, Hubei, Peoples R China
8.Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China
9.Chinese Acad Sci, Key Lab Syst Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China
10.Peking Univ, Dept Endocrinol & Metab, Peoples Hosp, Beijing 100871, Peoples R China
11.Shanghai Jiao Tong Univ, Dept Endocrinol & Metab, Shanghai Diabet Inst,Peoples Hosp 6, Shanghai Key Lab Diabet Mellitus,Shanghai Clin Ct, Shanghai 200030, Peoples R China
12.Fudan Univ, Inst Endocrinol & Diabetol, Huashan Hosp, Shanghai Med Coll, Shanghai 200433, Peoples R China
13.Huazhong Univ Sci & Technol, Dept Food Hyg & Nutr, Sch Publ Hlth, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
14.Huazhong Univ Sci & Technol, Minist Educ Key Lab Environm & Hlth, Sch Publ Hlth, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
15.Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Med Mol Biol, Sch Basic Med,Peking Union Med Coll, Beijing 100730, Peoples R China
16.Huazhong Univ Sci & Technol, Inst Occupat Med, Sch Publ Hlth, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
17.Anhui Med Univ, Inst Dermatol, Hosp 1, Hefei, Anhui, Peoples R China
18.Anhui Med Univ, Dept Dermatol, Hosp 1, Hefei, Anhui, Peoples R China
19.Minist Natl Sci & Technol, State Key Lab Incubat Base Dermatol, Hefei, Anhui, Peoples R China
20.Mt Sinai Sch Med, Dept Prevent Med, Charles R Bronfman Inst Personalized Med, New York, NY USA
21.Mt Sinai Sch Med, Dept Prevent Med, Child Hlth & Dev Inst, New York, NY USA
22.Shanghai Ctr Bioinformat Technol, Shanghai, Peoples R China
23.Shanghai Jiao Tong Univ, Coll Life Sci & Biotechnol, Shanghai 200030, Peoples R China
推荐引用方式
GB/T 7714
Li, Huaixing,Gan, Wei,Lu, Ling,et al. A Genome-Wide Association Study Identifies GRK5 and RASGRP1 as Type 2 Diabetes Loci in Chinese Hans[J]. DIABETES,2013,62(1):291-298.
APA Li, Huaixing.,Gan, Wei.,Lu, Ling.,Dong, Xiao.,Han, Xueyao.,...&AGEN-T2D Consortium.(2013).A Genome-Wide Association Study Identifies GRK5 and RASGRP1 as Type 2 Diabetes Loci in Chinese Hans.DIABETES,62(1),291-298.
MLA Li, Huaixing,et al."A Genome-Wide Association Study Identifies GRK5 and RASGRP1 as Type 2 Diabetes Loci in Chinese Hans".DIABETES 62.1(2013):291-298.
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